Incidence and Mortality of Adenovirus Infection After Pediatric Allogeneic SCT – A Comparison Between Bone Marrow and CD3/19 Depleted PBSC

Infection with human adenoviruses (ADV) can cause life-threatening infections in pts after allo-SCT and represents a major reason for transplant related mortality (TRM, in historical cohorts after haplo- SCT up to 30%). Graft manipulation by T-cell depletion affect immune reconstitution and can extend duration of impairment of immunity after SCT. Delayed reconstitution of immunity increases the risk for viral infections. New preparative regimens such as reduced intensity conditioning (RIC) followed by CD3/19 depleted PBSC transplant (3/19depl-PBSCT) try to overcome these limitations. To substantiate this we studied the incidence (inc.) and mortality of ADV infection after ped. allo-SCT overall and as a function of graft. 210 transplants have been performed in 200 ped. pts in Frankfurt between ‘05 and ‘11. Donor source was 3/19depl-PBSC (n=95) and BM (n=115). Median follow up was 13.9 mths. Weekly post-transpl. ADV-screening was conducted by qPCR in plasma, throats swabs and faeces. Inc. of ADV detection in any compartment at any time-point was 40.0% and sign. higher after 3/19depl-PBSCT compared to BMT; 49.5% vs 32.2% (p=0.016). Inc. was 26.7% <=d60, 20.6% d61 to 100 and 14.0% >d100. Cumulative inc. of 3y TRM (CI 3y TRM) due to ADV disease was 4.6% (3/19depl-PBSCT 6.9%, BMT 3.0%; n. sign.). In detail, 14.5% of pts (29/200) died due to non relapse mortality. Amongst these 29 pts, 16 (55.2%) were ADV pos.. ADV positivity was sign. more frequent after 3/19depl-PBSCT compared to BMT (84.6% vs 31.3%; p=0.008). Mortality due to ADV disease among TRM pts was 27.6% (3/19depl- PBSCT 38.5%, BMT 18.8%; n. sign.). Overall CI 3y TRM was sign. higher in ADV pos. (n=84) vs neg. (n=126) pts (28.7% vs 13.4%, p=0.03). Taken together, ADV was detected in every second pt after 3/19depl-PBSCT. Although the CI 3y TRM due to ADV disease was low (4.6%), post-transpl. ADV detection sign. increased the risk for subsequent TRM. In summary, ADV represents a severe threat to survival, particularly in pts after 3/19depl-PBSCT. Apparently, more rapid reconstitution of immunity in these pts compared to historical mega-dose CD34 transplants resulted in low mortality due to ADV disease in this high-risk group.